Tributyltin hydride-mediated synthesis of bicyclic carbocycles initiated by Et3B/O2

Article abstract of DOI:10.1080/00397910903219484

Synthesis of bicyclic carbocycles involving tributyltin hydride-mediated-carbonyl radical cyclization reaction at room temperature has been reported. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903219484

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Tributyltin Hydride–Mediated Synthesis
of Bicyclic Carbocycles Initiated by Et3B/
O2
Chandran Prakash a , Ganesan Gobi Rajeshwaran a & Arasambattu K.
Mohanakrishnan a
a Department of Organic Chemistry, University of Madras, Guindy
Campus, Chennai, India
Version of record first published: 17 Jun 2010.
To cite this article: Chandran Prakash, Ganesan Gobi Rajeshwaran & Arasambattu K. Mohanakrishnan
(2010): Tributyltin Hydride–Mediated Synthesis of Bicyclic Carbocycles Initiated by Et3B/O2 , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:14, 2097-2107
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Synthetic Communications1, 40: 2097–2107, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219484
TRIBUTYLTIN HYDRIDE–MEDIATED SYNTHESIS OF
BICYCLIC CARBOCYCLES INITIATED BY Et3B/O2
Chandran Prakash, Ganesan Gobi Rajeshwaran, and
Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras, Guindy Campus,
Chennai, India
Synthesis of bicyclic carbocycles involving tributyltin hydride–mediated a-carbonyl radical
cyclization reaction at room temperature has been reported.
Keywords: Bicyclic carbocycles; radical cyclization; tributyltin hydride; triethylborane
INTRODUCTION
The synthesis of highly functionalized bicyclic systems is an area of continued
interest to synthetic chemists because of the existence of these frameworks in many
naturally occurring compounds.[1] The use of triethylborane in air as an initiator of
radical-based processes has become increasingly popular in recent years.[2] Because
radical reactions can be initiated by this reagent at ambient temperature, it has found
widespread application, particularly in the stereoselective addition of alkyl radicals
to double bonds. To widen the scope of this methodology, the a-carbonyl radical
cyclization reaction was planned using triethylborane as an initiator. We have
recently reported[3] an efficient synthesis of angularly fused carbocycles via tandem
radical cyclization of a-carbonyl radical generated using azobisisobutyronitrile
(AIBN) as the radical initiator. Herein, we report the results on the synthesis of
bicyclic vinylic ketones, bicyclic skeleton of guanacastepene 1,[4] and agariblazeis-
pirol C 2[5] using Et3B=O2[6] as the radical initiator at room temperature (Scheme 1).
RESULTS AND DISCUSSION
In continuation of our studies to develop a facile and efficient method to syn-
thesize the bicyclic core skeleton of various natural products, the Bu3SnH-mediated
radical cyclization of a-bromo cycloalkanons are initiated. To this end, the
CuI-promoted 1,4-addition of 4-(trimethylsilyl)-3-butynyl magnesium bromide to
3-methyl-2-cyclohexen-1-one 3 followed by trapping of the resulting enolate with
chlorotrimethylsilane (TMSCl) afforded silyl-enol ether 4 in 86% yield, which on
Received April 24, 2009.
Address correspondence to Arasambattu K. Mohanakrishnan, Department of Organic Chemistry,
University of Madras, Guindy Campus, Chennai 600 025, India. E-mail: mohan_67@hotmail.com
2097

2098
C. PRAKASH, G. G. RAJESHWARAN, AND A. K. MOHANAKRISHNAN
Scheme 1. Natural products containing tricyclic carbocycles.
[7]
bromination using NaBr=FeCl3 delivered bromo compound 5 in good yield.
Radical cyclization of 5 was effected by Bu3SnH=AIBN via syringe addition pump
for 6 h in dry benzene at reflux to yield 6–5 bicyclic product 6 in 66% yield
(Scheme 2).
During the investigation of radical reactions at room temperature, we have
observed bicyclic product formation when Et3B=O2 was used as the radical initiator.
Typically, when bromo compound 5 was treated with tributyltin hydride using Et3B=
O2 as a radical initiator via syringe addition pump for 4 h, it afforded the expected
bicyclic product 6 in 62% yield (Scheme 3).
Scheme 2. Preparation of carbocycle 6 using tributyltin hydride and AIBN.
Scheme 3. Preparation of carbocycle 6 using tributyltin hydride and triethylborane.

SYNTHESIS OF BICYCLIC CARBOCYCLES
2099
Scheme 4. Preparation of carbocycle 10.
Encouraged by our success on 5-exo-dig mode of radical cyclization of 5, we
then examined the similar reaction of bromo compound 9, which furnished the
desired radical cyclized product 10 at room temperature using Et3B=O2 as a radical
initiator (Scheme 4).
Having established a method to construct the 6-5 bicyclic system, next we
turned our attention to the synthesis of 7-5 bicyclic core unit of guanacatsepene.
The required enone 11 was prepared using a known procedure.[8] The CuI-induced
1,4-addition of Grignard reagent to enone 11 followed by bromination using
NaBr=FeCl3 gave the bromo compound 13 in 78% yields. To our delight, upon treat-
ment of bromo compound 13 with tributyltin hydride and Et3B=O2 in benzene via
syringe addition pump for 4 h, radical cyclization occurred smoothly to give the
7–5 bicyclic system of guanacastepene 14 in 57% yield (Scheme 5).
Since the natural product, guanacatsepene, has a 7-6 bicyclic core, the required
a-bromo ketone 15 was prepared using an established procedure.[9] Surprisingly, the
radical cyclizations of bromo compound 15 using tribuyltin hydride–Et3B=O2 at
Scheme 5. Preparation of carbocycle 14.

2100
C. PRAKASH, G. G. RAJESHWARAN, AND A. K. MOHANAKRISHNAN
Scheme 6. Attempted preparation of carbocycle 16.
room temperature or tribuyltin hydride–AIBN at reflux were futile. Even though the
formation of a six-member ring under radical condition was reported[10] by Sha et al.,
in our case in both the conditions the expected radical cyclization product 16 was not
at all observed, and only the reduction product 17 was isolated (Scheme 6).
It should be noted that the bromo compounds 5, 9, and 13 underwent a smooth
radical cyclization at room temperature using Et3B=O2 as a radical initiator to afford
the respective bicyclic compounds in almost comparable yields. However, all
attempts to prepare the 7-6 bicyclic system 16 were unsuccessful; only a radical
quenched product was obtained. Therefore, we devised another synthetic route for
the synthesis of 7-6 bicyclic system using a ring-closing metathesis approach. In
recent years, olefin metathesis has emerged as a powerful tool for carbon–carbon
bond formation and has enabled the synthesis of rings of different sizes.[11] The
requisite enone 18 was prepared from 1,3-cyclohexanedione and allyl bromide by
adopting Stealey et al.’s[12] procedure. The established CuI-promoted 1,4-addition
of enone 18 using the procedure as mentioned afforded the silyl-enol ether 19 in
82% yield. Desilylation of 19 using NaOMe in tetrahydrofuran (THF) at room tem-
perature furnished the keto compound 20 as a pale yellow liquid. Treatment of diene
20 with 10 mol% of Grubb’s catalyst I in refluxing dicholoromethane (DCM) for 5 h
followed by column chromatographic purification furnished 6-7 bicyclic products 21
and 22 (2:1) in 56% and 27% yields, respectively (Scheme 7).
Scheme 7. Preparation of carbocycles 21 and 22.

SYNTHESIS OF BICYCLIC CARBOCYCLES
2101
In conclusion, we have presented radical cyclization methodology for the
synthesis of five- and six-membered bicyclic carbocycles via the intermediacy of
a-carbonyl radical generated using tributyltin hydride–Et3B=O2 at room tempera-
ture. The synthesis of 7–6 bicyclic system of guanacastepene was achieved using the
ring closing metathesis (RCM) approach. We hope the radical cyclization method-
ology performed herein at room temperature will be useful in the total synthesis of
carbocyclic natural products.
EXPERIMENTAL
All melting points were uncorrected. Reagents were purchased from commer-
cial sources and used as received without purification. Solvents were dried by stan-
dard procedures. Column chromatography was carried on silica gel (grade 60, mesh
size 230–400, Merck). Infrared (IR) spectra were recorded on a Shimadzu Fourier
1
transform (FT)–IR 8300 instrument. H and 13C NMR spectra were recorded in
CDCl3 using tetramethylsilane (TMS) as an internal standard on a Jeol 400 or 500
spectrometer at 400 and 100 or 125 MHz and on a Bruker-300 instrument
at 75 MHz, respectively. Mass spectra were recorded on a Jeol DX 303 HF
spectrometer. High-resolution mass analyses were performed using the electrospray
ionization (ESI) technique.
Representative Procedure for the Preparation of
4-(Trimethylsilyl)but-3-ynyl)cyclo-hex-1-enyloxy)trimethylsilane (4)
A solution of (4-bromobut-1-ynyl)trimethylsilane (3.71 g, 18.18 mmol) and
1,2-dibromoethane (0.1 mL) in dry THF (10 mL) was added to a stirred suspension
of Mg turnings (884 mg, 36.36 mmol) in THF (10 mL) under nitrogen at reflux with
a syringe pump (1 h). After the addition, the reaction mixture was heated to reflux
for 1 h to ensure the completion of the Grignard formation. It was then diluted
with dry THF (30 mL) and cooled to ꢀ78 ꢁC. CuI (3.46 g, 18.18 mmol) was added.
The reaction mixture was stirred for 30 min. 3-Methyl-2-cyclohexen-1-one 3
(800 mg, 7.27 mmol) in dry THF (5 mL) was added dropwise to this mixture, fol-
lowed by chlorotrimethylsilane (1.1 mL, 8.72 mmol) and triethylamine (1.31 mL,
9.45 mmol). The reaction mixture was warmed to room temperature, stirred for
12 h, and quenched with saturated NaHCO3 solution (10 mL). The resulting black
precipitate was filtered off and washed with hexane (40 mL). The combined organic
layer was washed with NaHCO3 solution (2 ꢂ 20 mL) and dried (K2CO3).
Filtration followed by removal of solvent gave crude silyl-enol ether 4 as a pale
yellow liquid (1.93 g, 86%). Crude product 4 was used for the next step without
further purification. IR (KBr): 2175 (alkyne), 1612 (alkene) cmꢀ1 1H NMR
.
(CDCl3, 400 MHz): d 4.41 (s, 1H, ꢀCH), 2.24–1.97 (m, 4H, ꢀCH2), 1.78–1.48
(m, 6H, ꢀCH2), 0.98 (s, 3H, ꢀCH3), 0.17 (s, 9H, ꢀCH3), 0.14 (s, 9H, ꢀCH3).
13C NMR (CDCl3, 100 MHz): d 138.4, 114.6, 107.3, 84.1, 39.5, 36.7, 35.2, 30.4,
26.8, 19.1, 15.3, 0.62, 0.09. Mass (m=z) % 308 (Mþ, 16), 293 (21), 243 (18), 184
(28), 163 (54), 113 (62), 82 (100).

2102
C. PRAKASH, G. G. RAJESHWARAN, AND A. K. MOHANAKRISHNAN
Representative Procedure for the Preparation of 2-Bromo-3-methyl-
3-(4-trimethylsilyl-3-butynyl)-1-cyclohexanone (5)
NaBr (535 mg, 5.19 mmol) was added to a solution of FeCl3 (1.68 g,
10.38 mmol) in acetonitrile (20 mL) and stirred at 0 ꢁC for 15 min. To this, a sol-
ution of silyl-enol ether 4 (1.6 g, 5.19 mmol) in acetonitrile (10 mL) was added
dropwise at 0 ꢁC. The reaction mixture was allowed to warm to room tempera-
ture and stirred for 4 h. It was then quenched (consumption of starting material
indicated by TLC) with saturated NH4Cl solution, and reaction mixture was
extracted with Et2O (2 ꢂ 20 mL). The organic layer was separated and washed
with saturated Na2S2O3 (2 ꢂ 10 mL) solution and water (20 mL) and then dried
(Na2SO4). Removal of solvent followed by flash-column chromatographic purifi-
cation (0.5% ethyl acetate in hexane to 1% ethyl acetate in hexane) afforded
bromo compound 5 (1.36 g, 83%) as a pale yellow liquid. IR (KBr): 2175
(alkyne), 1710 (CO), cmꢀ1.1H NMR (CDCl3, 400 MHz): d 4.42 and 4.22 (2s,
1H, ꢀCH), 2.24–2.13 (m, 4H, ꢀCH2), 1.89–1.76 (m, 2H, ꢀCH2), 1.72–1.52 (m,
4H, ꢀCH2), 0.96 and 0.92 (2s, 3H, ꢀCH3), 0.11 and 0.09 (2s, 9H, ꢀCH3). 13C
NMR (CDCl3, 100 MHz): d 206.5, 205.3, 107.6, 105.2, 86.5, 85.3, 54.2, 49.1,
46.5, 41.7, 41.2, 36.4, 35.8, 32.4, 32.7, 26.9, 25.2, 21.5, 20.3, 19.1, 15.4, 15.2,
0.13, 0.08. (1H & 13C NMR signals are more because of the diastereomeric mix-
ture.) Mass (m=z) % 300 [M ꢀ 15]þ, (13), 298 (13), (25), 284 (21), 223 (35), 175
(23), 134 (54), 82 (100).
Radical Cyclization Using Bu3SnH/AIBN (7aSꢃ)-Octahydro-7a-
methyl-3-((trimethylsilyl)methylene)inden-4-one (6)
A solution of Bu3SnH (0.51 mL, 1.90 mmol) in dry benzene (10 mL) contain-
ing AIBN (39 mg, 0.24 mmol) was added dropwise with a syringe pump to a sol-
ution of bromo compound 5 (500 mg, 1.59 mmol) in dry benzene (100 mL) under
nitrogen at reflux for 6 h. After addition, the reaction mixture was heated at
reflux for 1 h to ensure the completion of radical cyclization and then cooled
to room temperature. Benzene was removed in vacuo, and the residue was dis-
solved in Et2O (20 mL). A saturated KF solution (20 mL) was added. The result-
ing mixture was stirred at room temperature for 6 h. Then the organic layer was
separated and washed with saturated NaHCO3 solution (2 ꢂ 10 mL) followed by
brine (2 ꢂ 10 mL) and dried (MgSO4). Removal of solvent followed by flash col-
umn chromatographic purification (1% ethyl acetate in hexane to 2% ethyl acetate
in hexane) afforded bicyclic product 6 as a viscous liquid (248 mg, 66%). IR
1
(KBr): 1705 (CO), 1613 (alkene) cmꢀ1. H NMR (CDCl3, 300 MHz): d 5.84 and
5.27 (2s, 1H, ꢀCH), 2.89 (s, 1H, ꢀCH), 2.52–2.16 (m, 4H, ꢀCH2), 1.87–1.52
(m, 4H, ꢀCH2), 1.42–1.25 (m, 2H, ꢀCH2), 1.10 and 1.05 (2s, 3H, ꢀCH3), 0.14
and 0.11 (2s, 9H, ꢀCH3). 13C NMR (CDCl3, 75 MHz): d 212.8, 212.3, 160.1,
159.6, 123.9, 123.6, 70.9, 65.0, 45.5, 43.3, 42.3, 41.8, 39.3, 38.6, 33.5, 30.6, 27.4,
25.9, 23.6, 22.6, 19.3, 16.9, 0.10, 0.4. (1H & 13C NMR signals are more because
of the diastereomeric mixture.) Mass (m=z) % 236 (Mþ, 25), 221 (34), 182 (27),
154 (21), 125 (58), 82 (100).

SYNTHESIS OF BICYCLIC CARBOCYCLES
2103
General Procedure for Radical Cyclization Using Bu3SnH and Et3B/O2
(7aSꢃ)Octahydro-7a-methyl-3-((trimethylsilyl)methylene)inden-4-one (6)
A solution of bromo compound 5 (500 mg, 1.59 mmol) in dry benzene (30 mL)
was placed in a two-necked flask under oxygen atmosphere. To this, a 1 M solution
of Et3B in THF (1.1 mL, 2.38 mmol) was added, and then oxygen gas was bubbled
for 5 min. A solution of Bu3SnH (0.64 mL, 2.38 mmol) in dry benzene (10 mL) was
added via syringe pump over a period of 4 h and stirred at room temperature for
additional 1 h. Then the organic layer was separated and washed with saturated
NaHCO3 solution (2 ꢂ 10 mL) followed by brine (2 ꢂ 10 mL) and dried (MgSO4).
Removal of solvent followed by flash-column chromatographic purification (1%
ethyl acetate in hexane to 2% ethyl acetate in hexane) afforded bicyclic product 6
as a viscous liquid (0.23 g, 62%).
3,4-Dimethyl-3-(4-(trimethylsilyl)but-3-ynyl)cyclohex-1-
enylox)trimethylsilane (8)
The 1,4-addition was performed using enone 7 (750 mg, 6 mmol), Grignard
reagent [prepared from Mg (725 mg, 30.24 mmol), 4-bromo1-trimethylsilyl-1-butyne
(3.1 g, 15.10 mmol)], CuI (2.87 g, 15.1 mmol), TMSCl (0.92 mL, 7.30 mmol), and
Et3N (1.1 mL, 7.86 mmol) following the same procedure as that of 4 to afford crude
1
silyl-enol ether 8 (1.7 g, 86%) as a thick liquid. IR (KBr): 2173 (alkyne) cmꢀ1. H
NMR (CDCl3, 400 MHz): 4.50 (s, 1H, ꢀCH), 2.20–1.86 (m, 3H, ꢀCH2),
1.65–1.50 (m, 4H, ꢀCH2), 1.42–1.34 (m, 2H, ꢀCH2), 0.78 (d, J ¼ 5.3 Hz, 3H,
ꢀCH3), 0.76 (s, 3H, ꢀCH3), 0.09 (s, 9H, ꢀCH3), 0..08 (s, 9H, ꢀCH3). Mass (m=z)
%: 322 (Mþ, 15), 307 (24), 274 (19), 231 (34), 73 (100).
(7Sꢃ,7aR)-Octahydro-7,7a-dimethyl-3-((trimethylsilyl)-
methylene)inden-4-one (10)
Radical cyclization of 9 (500 mg, 1.51 mmol) was performed using Bu3SnH
(0.61 mL, 2.27 mmol) and 1 M solution of Et3B in THF (1.7 mL, 2.27 mmol) follow-
ing the same procedure as that of 6 to afford bicyclic product 10 (224 mg, 59%) as a
1
viscous liquid. IR (KBr): 1707 (ꢀCOꢀ), 1612 (alkene) cmꢀ1. H NMR (CDCl3,
400 MHz): d 5.88 and 5.35 (2 s, 1H, ꢀCH), 2.94(s, 1H, ꢀCH), 2.56–2.23 (m, 4H,
ꢀCH2), 1.92–1.37 (m, 5H, ꢀCH2 & ꢀCH), 1.18 (2d, J ¼ 5.3 Hz, 3H, ꢀCH3), 1.13
and 1.07 (2 s, 3H, ꢀCH3), 0.15 and 0.12 (2 s, 9H, ꢀCH3). 13C NMR (CDCl3,
100 MHz): d 213.4, 212.8, 161.3, 160.5, 124.6, 123.9, 71.4, 66.2, 45.8, 44.1, 43.5,
42.1, 39.7, 38.3, 34.8, 31.3, 28.2, 26.5, 24.1, 23.8, 20.2, 19.4, 18.7, 17.4, 0.11, 0.05.
(1H & 13C NMR signals are more because of the diastereomeric mixture.) Mass
(m=z) % 250 (Mþ, 25), 235 (28), 220 (38), 185 (22), 163 (24), 136 (43), 82 (100).
Trimethyl(3-methyl-3-(4-(trimethylsilyl)but-3-ynyl)cyclohept-1-
enyloxy)silane (12)
The 1,4-addition was performed using enone 11 (650 mg, 5.24 mmol), Grignard
reagent [prepared from Mg (630 mg, 26.20 mmol), 4-bromo1-trimethylsilyl-1-butyne

2104
C. PRAKASH, G. G. RAJESHWARAN, AND A. K. MOHANAKRISHNAN
(2.68 g, 13.10 mmol)], CuI (2.50 g, 13.10 mmol), TMSCl (0.80 mL, 6.30 mmol), and
Et3N (0.95 mL, 6.81 mmol) following the same procedure as that of 4 to afford crude
silyl-enol ether 12 (1.42 g, 84%) as a thick liquid. IR (KBr): 2174 (alkyne), 1616
1
(alkene) cmꢀ1. H NMR (400 MHz, CDCl3): d 4.39 (s, 1H, ꢀCH), 2.34–2.12 (m,
4H, ꢀCH2), 1.91–1.72 (m, 6H, ꢀCH2), 1.64–1.48 (m, 2H, ꢀCH2), 0.96 (s, 3H,
ꢀCH3), 0.18 (s, 9H, ꢀCH3), 0.13 (s, 9H, ꢀCH3). 13C NMR (125.7 MHz, CDCl3)
d 126.1, 116.3, 107.5, 85.1, 39.7, 37.5, 36.8, 31.8, 28.4, 26.2, 19.8, 15.2, 0.86, 0.22.
MS (EI) m=z (%): 322 (Mþ, 16), 307 (11), 226 (29), 198 (14), 158 (23), 73 (100). Crude
product 12 was used for the next step without further purification.
2-Bromo-3-methyl-3-(4-trimethylsilyl-3-butynyl)-1-cycloheptanone (13)
Bromination using compound 12 (1.30 g, 4.03 mmol), NaBr (415 mg,
4.03 mmol), and FeCl3 (1.31 g, 8.07 mmol) followed the same procedure as that of
5 to afford the bromo compound 13 (1.03 mg, 78%) as a yellow liquid. IR (KBr):
1
2173 (alkyne), 1706 (CO) cmꢀ1. H NMR (400 MHz, CDCl3): d 4.35 & 4.26 (2s,
1H, ꢀCH), 2.51–2.27 (m, 2H, ꢀCH2), 2.21–2.07 (m, 4H, ꢀCH2), 1.92–1.78 (m,
2H, ꢀCH2), 1.74–1.35 (m, 4H, ꢀCH2), 0.98 and 0.91 (2s, 3H, ꢀCH3), 0.16 and
0.12 (2s, 9H, ꢀCH3). 13C NMR (100 MHz, CDCl3): d 205.6, 204.8, 108.2, 107.3,
86.3, 85.2, 72.4, 71.7, 71.1, 70.3, 58.5, 54.3, 49.1, 43.2, 38.8, 30.6, 29.7, 28.6, 25.3,
22.2, 19.6, 19.0, 18.5, 17.6, 0.14, 0.09. MS (EI) m=z (%): 330 ([M þ 2]þ, 8), 328
(Mþ, 8), 304 (6), 231 (22), 193 (4), 153 (23), 73 (100).
(8aSꢃ)-Octahydro-8a-methyl-3-(trimethylsilyl)methylene)
azulen-4(5H)-one (14)
Radical cyclization of 13 (800 mg, 2.43 mmol) was performed using Bu3SnH
(1.1 mL, 3.65 mmol) and 1 M solution of Et3B in THF (2.15 mL, 3.65 mmol) follow-
ing the same procedure as that of 6 to afford bicyclic product 14 (347 mg, 57%) as a
.
viscous liquid. IR (film) 1701 (CO), 1613 (alkene) cmꢀ1 1H NMR (400 MHz,
CDCl3): d 5.63 & 5.26 (2s, 1H, ꢀCH), 3.54 & 3.30 (2s, 1H, ꢀCH), 2.42–2.38 (m,
4H, ꢀCH2), 1.72–1.59 (m, 6H, ꢀCH2), 1.48–1.45 (m, 2H, ꢀCH2), 1.07 (s, 3H,
ꢀCH2), 0.12 & 0.07 (2s, 9H, ꢀCH3). 13C NMR (100 MHz, CDCl3): d 212.3,
212.1, 160.0, 159.5, 123.9, 123.6, 70.9, 65.0, 45.5, 43.3, 42.3, 41.8, 39.3, 38.6, 37.7,
37.5, 34.5, 31.0, 27.5, 23.6, 22.6, 22.5, 19.3, 16.8, 0.36, 0.16. HRMS: calcd. for
C15H26OSi 250.1753; found 250.1762.
3-Methyl-3-(5-(trimethylsilyl)pent-4-ynyl)cycloheptanone (17)
Radical cyclization of 15 (750 mg, 2.19 mmol) was performed using Bu3SnH
(0.71 mL, 2.68 mmol) and 1 M solution of Et3B in THF following the same pro-
cedure as that of 6 to afford radical quenched product as a viscous liquid (0.35 g,
1
60%). IR (KBR): 2175 (alkyne), 1701 (CO) cmꢀ1. H NMR (400 MHz, CDCl3):
d 2.56–2.48 (m, 2H, ꢀCH2), 2.37–2.21 (m, 2H, ꢀCH2), 2.15–1.72 (m, 6H, ꢀCH2),
1.86–1.42 (m, 5H, ꢀCH2), 1.19 (s, 3H, ꢀCH3), 0.13 (s, 9H, ꢀCH3). 13C NMR
(100 MHz, CDCl3): d 210.2, 106.4, 85.3, 55.1, 46.7, 37.5, 34.2, 31.6, 27.5, 25.8,
24.1, 19.4, 15.8, 0.17. HRMS: calcd. for C16H28OSi 264.1909; found 264.1916.

SYNTHESIS OF BICYCLIC CARBOCYCLES
2105
2-Allyl-3-methyl-3-pent-3-enyl)cyclohex-1-enyloxy)trimethyl Silane (19)
The 1,4-addition of 2-allyl-3-methylcyclohex-2-enone 18 (750 mg, 5.0 mmol) was
performed using Grignard reagent [prepared from Mg (600mg, 25.0 mmol), 5-
bromopen-2-ene (1.86 g, 12.5mmol)], CuI (2.38 g, 12.5mmol), TMSCl (0.76 mL,
6.0 mmol), and Et3N (0.90mL, 6.50mmol) following the same procedure as that of
2 to afford crude silyl-enol ether 19 (1.19g, 82%) as a thick liquid. 1H NMR (CDCl3,
400 MHz): d 5.81–5.73 (m, 1H, ꢀCH), 5.46–5.40 (m, 2H, ꢀCH2), 5.11–4.90 (m, 2H,
ꢀCH2), 2.26–1.97 (m, 8H, ꢀCH2), 1.83–1.67 (m, 4H, ꢀCH2) 1.61–1.22 (m, 3H,
ꢀCH3), 0.98 (s, 3H, ꢀCH3), 0.15 (s, 9H, ꢀCH3). 13C–NMR (CDCl3, 100 MHz): d
146.3, 144.9, 132.1, 124.6, 121.2, 116.6, 39.2, 34.9, 32.7, 30.2, 27.7, 26.7, 19.1, 18.3,
15.4, 0.24. Mass (m=z) % 292 (Mþ, 31), 248 (25), 184 (34), 142 (46), 93(64), 78
(100). Crude product 15 was used for the next step without further purification.
2-Allyl-3-methyl-3-(pent-3-enyl)cyclohexanone (20)
A solution of silyl-enol ether 19 (0.50 g, 1.71 mmol) in dry THF (15 mL) was
added dropwise to the stirred suspension of NaOMe (185 mg, 3.42 mmol) in dry
THF (15 mL) at 0 ꢁC. Then it was raised to room temperature and stirred for 2 h.
The reaction mixture was quenched by adding ice water (30 mL) and extracted with
ether (2 ꢂ 15 mL). The combined extracts were washed with brine (2 ꢂ 20 mL) and
dried (Na2SO4). Removal of the solvent followed by flash-column chromatographic
purification (silica gel, 2.5% ethyl acetate in hexane) afforded keto compound 20
1
(294 mg, 78%) as pale yellow liquid. IR (KBr): 1706 (CO), 1632 (alkene) cmꢀ1. H
NMR (CDCl3, 400 MHz): d 5.56–5.51 (m, 1H, ꢀCH), 5.41–5.38 (m, 2H, ꢀCH),
5.16–5.22(m, 2H, ꢀCH2), 2.45–2.16 (m, 4H, ꢀCH2), 2.11–1.81 (m, 5H, ꢀCH2&
ꢀCH), 1.72–1.32 (m, 5H, ꢀCH2& ꢀCH), 1.12–0.98 (m, 32H, ꢀCH), 0.81 (s, 3H,
ꢀCH3). 13C NMR (CDCl3, 100 MHz): d 212.5, 133.2, 130.6, 124.7, 118.1, 60.2,
56.4, 42.3, 35.6, 34.2, 31.8, 25.1, 23.4, 17.5, 15.7. Mass (m=z) % 220 (Mþ, 23), 206
(18), 187 (34), 143(54), 84 (100).
(4aSꢃ,9aSꢃ)-2,3,4,4a,5,6,9,9a-Octahydro-4a-methylbenzo(7)
annulen-1-one (21 and 22)
The diene 20 (200 mg, 0.91 mmol) was dissolved in DCM (10 mL), and a
solution of 10 mol% of Grubbs’s first-generation catalyst in dry DCM (5 mL) was
slowly added under a nitrogen atmosphere. The resulting solution was refluxed for
5 h. Then, the reaction mixture was filtered, and the solvent was removed under
vacuo. The residue was subjected to flash-column chromatographic purification
(silica gel; 1.3% ethyl acetate in hexane to 2.5% ethyl acetate in hexane), which
furnished the (7-6) bicyclic systems 21 and 22 as viscous liquid.
(Z,4aS,9aR)-2,3,4,4a,5,6,9,9a-Octahydro-4a-methylbenzo[7]
annulen-1-one (21)
Yield: 91 mg (56%). IR (KBr): 1710 (CO), 1658 (alkene) cmꢀ1
.
1H NMR
(CDCl3, 400 MHz): d 5.69–5.62 (m, 2H, ꢀCH), 2.44–2.41 (m, 1H, ꢀCH),

2106
C. PRAKASH, G. G. RAJESHWARAN, AND A. K. MOHANAKRISHNAN
2.34–2.27 (m, 2H, ꢀCH2), 2.25–2.10 (m, 4H, ꢀCH2), 2.04–1.80 (m, 2H, ꢀCH2),
1.79–1.73 (m, 2H, ꢀCH2), 1.54–1.39 (m, 2H, ꢀCH2), 0.78 (s, 3H, ꢀCH3). 13C
NMR (CDCl3, 100 MHz): d 213.1, 132.0, 130.2, 57.3, 41.7, 39.6, 35.7, 27.2, 25.2,
23.4, 22.7, 18.4. Mass (m=z) % 178 (Mþ, 12), 163 (22), 119 (38), 107 (25), 93 (26),
81 (48), 79 (100).
(Z,4aS,9aS)-2,3,4,4a,5,6,9,9a-Octahydro-4a-methylbenzo[7]
annulen-1-one (22)
Yield: 43 mg (27%). IR (KBr): 1708 (CO), 1661 (alkene) cmꢀ1 1H NMR
.
(CDCl3, 400 MHz): d 5.60–5.58 (m, 2H, ꢀCH), 2.47–2.43 (m, 1H, ꢀCH),
2.39–2.36 (m, 2H, ꢀCH2), 2.25–2.10 (m, 4H, ꢀCH2), 1.96–1.87 (m, 2H, ꢀCH2),
1.85–1.66 (m, 2H, ꢀCH2), 1.43–1.30 (m, 2H, ꢀCH2), 0.93 (s, 3H, ꢀCH3). 13C
NMR (CDCl3, 100 MHz): d 214.1, 131.4, 128.8, 59.2, 39.8, 39.6, 35.7, 27.2, 25.3,
23.1, 21.8.
ACKNOWLEDGMENTS
The authors thank the Council of Scientific and Industrial Research (CSIR),
New Delhi [01(1765)=02=EMR-II], for a financial support. C. P. thanks CSIR for
a CSIR senior research fellowship. The authors thank the Department of Science
and Technology, Funding for Infrastructure in Science and Technology, for use of
the 300-MHz NMR facility.
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